Schizophrenic psychosis: a contraindication for treatment of hepatitis C with interferon alpha?

Depressive or psychotic symptoms are a well known side-effect of interferon alpha (INF-alpha). Therefore, the questions arises whether a chronic psychosis should be considered a contraindication for the treatment of active hepatitis C with INF-alpha. We report on a 38-year-old woman with a chronic schizophrenic psychosis, who acquired chronic aggressive hepatitis C. Considering the young age of the woman, the potential risk of developing a hepatocellular carcinoma and the result of the liver biopsy, treatment with interferon alpha 2 b (3x5 million IU/week) was started. The patient was seen three times a week, her psychiatric condition was monitored using the positive and negative symptoms score (PANSS). No signs of psychotic or depressive symptoms appeared during INF-alpha therapy. During the first 6 months the liver enzymes dropped slowly but the virus load was increasing. After adding ribavirin to the therapy, the liver enzymes dropped again, and the PCR carried out 9 months after initiation and 6 months after the end of the 12 months INF-alpha treatment did not detect any virus RNA. This positive result should encourage prospective studies including patients with these two diagnoses on whether patients benefit from INF-alpha.     

Is late onset depression a prodrome to dementia?

BACKGROUND: Recent research suggests there are clinical and biological differences between late onset depression (LOD) and early-onset depression (EOD). OBJECTIVES: In this paper we review clinical, epidemiological, structural neuroimaging and genetic investigations of late life depression that have been performed over the past two decades and offer evidence that LOD is often a prodromal disorder for dementia. RESULTS: LOD patients are more likely to have cognitive impairment and to have more deep white matter lesions (DWMLs). Evidence concerning cortical and temporal lobe atrophy is conflicting, while the ApoE 4 allele is not associated with LOD. CONCLUSIONS: It is likely that LOD is not a prodrome for a particular type of dementia, but the majority of patients who do develop dementia will acquire Alzheimer's disease (AD) or a vascular dementia, as these are by far the most common causes of dementia. This issue requires further clarification with follow-up of patients over the long term.     

Is major depression a neurologic disorder with psychiatric symptoms?

In the last decade, multiple investigator groups have identified structural changes of various neuroanatomic structures in patients with idiopathic major depression and bipolar disorders. Using high-resolution MRI of the brain and functional neuroimaging studies (i.e., PET, SPECT), researchers have described decreases in the volume of hippocampal formation, amygdala, entorhinal cortex, various frontal lobe structures, and basal ganglia, in addition to abnormal cerebral blood flow and metabolic activity in these structures as well as in thalamic nuclei. Similar structural and functional changes have been identified in patients with depression associated with a variety of neurologic disorders (i.e., stroke, Parkinson's disease, epilepsy, Alzheimer's dementia). In addition, recent data have shown that depression is a risk factor for the development of several neurologic disorders, including epilepsy, stroke, and Parkinson's disease and bears a negative impact on the course and outcome of most neurologic disorders. This article reviews these data and provides evidence that major depressive and bipolar disorders may in fact be neurologic disorders with psychiatric symptoms.     

Do health professionals' attitudes interfere with the treatment of depression?

Might the attitudes of health care professionals help to explain why most persons with a depressive disorder do not receive adequate care? To assess this question, the authors surveyed the faculty and staff of a midwestern university. One hundred percent of the social workers who responded found psychotherapy or counseling to be extremely or quite effective in treating persons with a major depressive episode, compared to 55% of the psychologists and 31% of the psychiatrists. For medication, the corresponding figures were 88% of psychiatrists, 64% of psychologists, and 46% of social workers. Many respondents noted problems with interprofessional communication, while most psychiatrists felt that individuals treated by two or more professionals for their depression usually receive poorer care. If future studies indicate that nonmedical therapists who view antidepressants as relatively ineffective are less likely to refer depressed clients for medication evaluation, these findings might help to explain why many depressed individuals who could benefit from medication do not receive it. Concerns about interprofessional communication, as well as psychiatrists' beliefs about the quality of care received by persons treated by more than one professional, might also explain why joint treatment occurs less often than would be desirable. The authors discuss some of the implications that these findings may have for the education of health care professionals.     

Is inadequate family history a barrier to diagnosis in CADASIL?

OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) has typical clinical features that include stroke, migraine, mood disturbances and cognitive decline. However, misdiagnosis is common. We hypothesized that family history is poorly elicited in individuals presenting with features of CADASIL and that enquiry into family history of all four cardinal manifestations of CADASIL is superior to elicitation of family history of premature stroke alone in raising the diagnostic possibility of CADASIL. MATERIALS AND METHODS: Retrospective review of family histories at presentation in 40 individuals with confirmed CADASIL was performed through structured interview in a Neurovascular Genetics clinic (182 first-degree and 242 second-degree relatives identified). Family history obtained from structured interview was compared to family history initially documented at presentation. RESULTS: At initial presentation, 30% of individuals were inaccurately documented to have no family history of significant neurological illness. Thirty-five per cent of patients had an initial alternative diagnosis. Initial inaccurate documentation of negative family history was more frequent in individuals with an initial alternative diagnosis. After structured interviews, 34% of 182 first-degree and 35% of 242 second-degree relatives of CADASIL patients had history of stroke (16% of first-degree relatives had stroke before the age of 50 years). Forty-three per cent of first-degree and 28% of second-degree relatives had migraine, mood disturbance or cognitive decline. CONCLUSIONS: A false-negative family history was commonly documented in individuals presenting with features of CADASIL and was associated with initial misdiagnosis. Restriction of family history to premature stroke alone is probably inadequate to identify affected CADASIL pedigrees.     

Is major depression a cognitive disorder?

This is a review of cognitive abilities in major depression, which is associated with attention problems, memory deficit and wide impairment in executive functions. Depressed patients show two major cognitive biases: excessive processing of negatively valenced emotional stimuli; and increased self-focus. Both of these biases help to facilitate the integration of negative self-related information in depressed patients and to maintain their negative mood. Brain imaging studies suggest that this cognitive impairment is characterized by abnormal cooperation between the cognitive and limbic networks involved in cognitive control and self-referential processing. In general, depression is a disorder of multiple networks with emotional, cognitive and emotional symptoms. Among these symptoms, cognition is a major determinant of functional and social outcomes.     

Is it time to reassess the BDNF hypothesis of depression?

The brain-derived neurotrophic factor (BDNF) hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and that its restoration may underlie the therapeutic efficacy of antidepressant treatment. While this theory has received considerable experimental support, an increasing number of studies have generated evidence which is not only inconsistent, but also directly contradicts the hypothesis. This article provides a critical review of the clinical and preclinical studies which have been responsible for this controversy, outlining pharmacological, behavioural and genetic evidence which demonstrates the contrasting role of BDNF in regulating mood and antidepressant effects throughout the brain. I will also review key studies, both human and animal, which have investigated the association of a BDNF single-nucleotide polymorphism (Val66Met) with depression pathogenesis, and detail the number of inconsistencies which also afflict this novel area of BDNF research. The article will conclude by discussing why now is a critical time to reassess the original BDNF hypothesis of depression, and look towards the formation of new models that can provide a more valid account of the complex relationships between growth factors, mood disorders and their treatment.     

Is 18F-FDG-PET suitable to predict clinical response to the treatment of geriatric depression? A systematic review of PET studies

Background: Geriatric depression is one of the most common psychiatric disorders in later life. It differs from earlier depression in its presentation, etiology, risk factors, protective factors and outcome. Positron emission tomography (PET) can be used to detect changes in neural circuitry in neuropsychiatric disorders, and several authors have assessed its role in the diagnosis and follow-up of patients with geriatric depression. We reviewed the current evidence on the use of fluorine-18-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) in geriatric depressed patients to find predictors of treatment response.

Methods: We searched PubMed/MEDLINE, Scopus, Embase, Cochrane Library, CINAHL and the PsycINFO databases to find relevant peer-reviewed articles on PET in geriatric depression using the search terms (‘PET’ or ‘positron emission tomography’) and (‘mood’ or ‘affective disorder’ or ‘affective disorders’ or ‘depression’ or ‘dysthymia’ or ‘seasonal affective disorder’).

Results: Eleven articles comprising 128 patients were included. We extracted data on glucose uptake of depressed patients and controls at baseline and after different types of intervention (total sleep deprivation followed by a recovery sleep and treatment with selective serotonin reuptake inhibitors).

Conclusions: ¹⁸F-FDG-PET showed significant alterations of glucose uptake in several brain areas, in particular the anterior cingulate cortex, which showed reduced metabolism after treatment, and was a predictor of treatment response.     

Is co-morbid depression adequately treated in patients repeatedly referred to specialist medical services with symptoms of a medical condition?

ObjectivePatients with a medical condition and co-morbid depression have more symptoms and use more medical services. We aimed to determine the prevalence of depression and the adequacy of its treatment in patients who had been repeatedly referred from primary to specialist medical care for the assessment of a medical condition.MethodsAll patients who had at least three referrals to medical and surgical specialists for an assessment of symptoms attributed to a medical condition, over a five year period from five primary care practices in Edinburgh, UK were identified using a referral database and review of records. Participants were sent a questionnaire which included the PHQ-9 depression scale and additional questions about depression during the preceding 5 years. Details of treatment for depression were obtained from primary care records.ResultsQuestionnaires were sent to 230 patients and returned by 162 (70.4%). Forty-one (25.3%) had a PHQ-9 score of 10 or more and hence probable current depressive disorder. An additional 36 (22.2%) reported depression in the previous 5 years. Only eight (19.5%) of those reporting current depression and 20 (26%) of the 77 patients reporting previous depression had received minimally adequate treatment for it.ConclusionWhilst we know that patients with medical conditions are often depressed and that such co-morbid depression is often undertreated, we have found that it is undertreated even in patients repeatedly referred to medical specialists. Better assessment and management of depression in such patients could both improve patients' quality of life and reduce the cost of care.     

Inflammation and depression: Is there a causal connection with dementia?

Epidemiological studies show that there is a correlation between chronic depression and the likelihood of dementia in later life. There is evidence that inflammatory changes in the brain are pathological features of both depression and dementia. This suggests that an increase in inflammation-induced apoptosis, together with a reduction in the synthesis of neurotrophic factors caused by a rise in brain glucocorticoids, may play a role in the pathology of these disorders. A reduction in the neuroprotective components of the kynurenine pathway, such as kynurenic acid, and an increase in the neurodegenerative components, 3- hydroxykynurenine and quinolinic acid, contribute to the pathological changes. Such changes are postulated to cause neuronal damage and thereby predispose chronically depressed patients to dementia.     

Can long-term treatment with antidepressant drugs worsen the course of depression?

BACKGROUND: The possibility that antidepressant drugs, while effectively treating depression, may worsen its course has received inadequate attention. METHOD: A review of the literature suggesting potential depressogenic effects of long-term treatment with antidepressant drugs was performed. A MEDLINE search was conducted using the keywords tolerance, sensitization, antidepressive agents, and switching. This was supplemented by a manual search of Index Medicus under the heading "antidepressant agents" and a manual search of the literature for articles pointing to paradoxical effects of antidepressants. RESULTS: A number of reported clinical findings point to the following possibilities: very unfavorable long-term outcome of major depression treated by pharmacologic means, paradoxical (depression-inducing) effects of antidepressant drugs in some patients with mood and anxiety disturbances, antidepressant-induced switching and cycle acceleration in bipolar disorder, occurrence of tolerance to the effects of antidepressants during long-term treatment, onset of resistance upon rechallenge with the same antidepressant drug in a few patients, and withdrawal syndromes following discontinuation of mood-elevating drugs. These phenomena in susceptible individuals may be explained on the basis of the oppositional model of tolerance. Continued drug treatment may recruit processes that oppose the initial acute effects of a drug and may result in loss of clinical effect. When drug treatment ends, these processes may operate unopposed, at least for some time, and increase vulnerability to relapse. CONCLUSION: The possibility that antidepressant drugs may worsen the course of depression needs to be tested, even though its scientific exploration is likely to encounter considerable methodological and ideological difficulties. The clinical implications of this hypothesis in depression are considerable. Antidepressant drugs are crucial in the treatment of major depressive episodes. However, appraisal of paradoxical effects that may occur in susceptible patients during long-term treatment may lead to more effective use of the drugs.     

Is depression related to subsequent diabetes mellitus?

OBJECTIVE: To compare the risk of developing diabetes mellitus (DM) in the general population between subjects who had a depression and subjects who never had a depression. METHOD: Retrospective cohort design. People with depression were diagnosed with a depression between 1975 and 1990; controls never had a depression. Both groups were followed for a diagnosis of type II diabetes until 2000. Data on 1334 depressed and 66 670 non-depressed subjects were available from a large general practice-based database. RESULTS: No overall relation was found, but among males below age 50 there was a 78% increase in the rate of development of DM compared with non-depressed patients (hazard ratio 1.78, 95% CI: 1.21-2.62). CONCLUSION: Depression in males between the age of 20 and 50 years is related to an increased risk of developing DM.     

The pharmacologic treatment of depression: is gender a critical factor?

BACKGROUND: In the medical literature, there is a lack of sex-specific information regarding the efficacy, metabolism, and side effects associated with psychopharmacologic treatment. In part, this lack results from the historic underinclusion of women in clinical trials during early drug development, but it also occurs because investigators of treatment and metabolic studies do not routinely analyze results according to sex. In 1993, the U.S. Food and Drug Administration (FDA) announced changes that encourage the inclusion of women in early pharmacokinetic studies and emphasize the need for subset analyses using sex and age parameters. In conjunction with advances in basic science regarding drug metabolism, these modifications have led to modest increases in information regarding sex differences in drug metabolism and efficacy. In this article, current information regarding potential sex differences in the pharmacotherapy of major depressive disorder is reviewed. DATA SOURCES: A MEDLINE search was conducted using the terms antidepressants, sex-factors, gender differences, and women for the years 1966 to 2000. DATA SYNTHESIS AND CONCLUSIONS: There are data supporting sex differences in the activity of various antidepressant-metabolizing enzymes. However, there is a paucity of investigation regarding how these differences might translate into differences in clinical efficacy. Notably, there is little work using existing databases to perform the subgroup analyses recommended by the FDA. The widespread dissemination of such work is needed, and, if conducted, investigations in this area have the potential to enhance psychopharmacologic treatment for both men and women.